The antigens of the major histocompatibility complex (MHC) participate in stereospecific molecular recognition events that are central to the functions of the cellular immune system. Antigen receptors on the surface of cytotoxic T-lymphocytes recognize and destroy transformed or virally infected cells only when those cells present both foreign antigens and the appropriate MHC molecules. In tissue graft rejection, MHC molecules themselves recognize foreign MHC molecules. A strong structural and evolutionary relationship between the cellular and humoral immune systems is implied by the existence of strong structural similarities between the immunoglobulins and parts of the MHC antigens. The goal of this project is to refine and extend to high resolution our knowledge of the three-dimensional structure of Beta2-microglobulin, the lighter of the two polypeptide chains making up the MHC class I antigens. The project will include collection of high-resolution diffraction data from crystals of bovine Beta2-microglobulin, combination of these data with both model and multiple isomorphous replacement phases based on our current 2.95 Angstrom resolution model of the protein, and restrained crystallographic refinement. In molecular model building experiments aided by computer graphic techniques, the refined high resolution model of Beta2-microglobulin will be combined with the known chemical structures of MHC heavy chains in order to develop a working model of the MHC antigen complex. This work should provide considerable insight into the evolutionary relationships between the immunoglobulins and the molecules of the MHC as well as into the role of Beta2-microglobulin in the function of the MHC antigens.